Boards as well as cards can be "universal", supporting both 3.3V and 1.5V signalling for 1x/2x and 4x/8x modes respectively.

Recent boards are NOT universal anymore, only supporting 1.5V signalling. Cards that are 3.3V-only (1x/2x-ONLY cards) will neither fit nor work. (That's what the key tab and notch are for; if they don't line up, you can't insert the card ... because it wouldn't work anyway.)

There are some select recent graphics chips that don't support 3.3V signalling anymore, e.g. ATI Radeon 9600, 9800 and X800 chip families. These won't fit or work in 1x/2x-ONLY mainboards. Others, like the 92X0 family, support both signalling voltage levels and work everywhere.